We read with interest the article recently published in HEPATOLOGY, 1 which suggested that heterozygosity for hemochromatosis C282Y mutation could be associated with more fibrosis in patients with chronic active hepatitis (CAH) owing to hepatitis C virus (HCV). Liver iron accumulation has been observed in patients with HCV infection, and could negatively influence the natural course of HCV-related liver disease. 2 Recently, a homozygous missense mutation, C282Y, within the HFE gene located on the chromosome 6, was found to be present in 82% to 100% of the patients with genetic hemochromatosis. 3,4 The ability to detect this mutation on DNA extracted from peripheral blood cells allows the assessment of its role in diseases associated with liver iron accumulation. We studied 209 consecutive patients with histologically proven CAH caused by HCV (131 men, 78 women, mean age 44.3 Ϯ 12.0 years) including 19 patients with cirrhosis (9.1%). Genomic DNA was extracted from peripheral leukocytes by standard methods. The C282Y mutation was screened for by restriction enzyme analysis of polymerase chain reaction-amplified products and by Rsa I digestion as described. 3 Histological fibrosis score was determined according to METAVIR classification. One patient was found to be homozygous for the C282Y mutation, with marked iron overload similar to that reported in genetic hemochromatosis and was therefore excluded for the assessment of the relationship between fibrosis and genotype at the HFE locus. The relationship between the C282Y mutation and fibrosis is shown in Table 1. The overall prevalence of heterozygous state for C282Y mutation (10.6%) was similar to that reported in the general population 1,3 and was not related to the degree of fibrosis. In addition, the prevalence of heterozygosity for C282Y mutation did not differ in patients with or without cirrhosis (15.8% vs. 10.2%, respectively, P ϭ .71). Thus, in our experience based on a large number of patients, heterozygosity for C282Y was not related to the severity of fibrosis. The relatively small number of patients who were heterozygous for C282Y in the study of Smith et al. 1 could explain the discrepancy with our data. Our data are consistent with heterozygosity for C282Y having no influence on liver iron accumulation. 5 CHRISTOPHE HE ´ZODE, M.